Macrophages may be the primary anti-neoplastic surveillance cells, especially the alveolar macrophages, which may be the most important defense mechanism protecting the lung from neoplastic growth as well as invading microbes. Conventional and specific pathogen-free (SPF) newborn colostrum-fed piglets have high numbers of neutrophils infiltrating the lung within 12 hr after birth and are replaced with large numbers of alveolar macrophages within a week. However, the germfree colostrum-deprived immunologically "virgin" piglets have absolutely no alveolar macrophages. Therefore, the germfree piglets present a unique opportunity to us to investigate: 1) ontogenic development and differentiation of alveolar macrophages in the controlled environment starting from zero level; 2) characterization of the nature of effector cells for natural cytotoxicity, antibody-dependent cellular cytotoxicity (ADCC) and complement (C3)-dependent cellular cytotoxicity (C3DCC) against various targets (syngeneic, allogenic and xenogeneic targets; tumor cells or transformed cells vs. untransformed cells); and 3) factors influencing the development and differentiation of alveolar macrophages and factors affecting their effector functions against target cells. Investigations on ontogenic development, differentiation of alveolar macrophages and regulatory mechanisms of their cytolytic and cytostatic effector functions may eventually lead to manipulation or control of alveolar macrophages against invading cells to confer on the host a better survival advantage.